巴丹、易卫杀在大鼠胃匀浆中生物转化的研究

建立了胃匀浆中巴丹、易卫杀的ＧＣ－ＦＰＤ测定方法，并用此方法观察了巴丹、易卫杀在大鼠胃匀浆中的转化。添加巴丹的胃匀浆样品，经Ｎａ２Ｓ溶液转化生成沙蚕毒素，其回收率为１０３．１％［ｎ＝４，ＲＳＤ（％）＝０．７３］；添加易卫杀的胃匀浆样品，其回收率为１００．５％［ｎ＝４，ＲＳＤ（％）＝０．５４］。在大鼠胃匀浆中分别添加巴丹、易卫杀后，１ｍｉｎ时，分别有４９．７％和２８．８％的巴丹、易卫杀转化成沙蚕毒素；至１０ｍｉｎ时，加入的巴丹及易卫杀大部分转化生成沙蚕毒素。结果显示，巴丹和易卫杀在大鼠体内极易转化成沙蚕毒素。     

经口灌胃杀虫双在大鼠体内代谢动力学研究

建立了全血中沙蚕毒素含量测定方法。沙蚕毒素回收率为80.0％～95.0％，平均为85.3％（n=8），相对标准差为5.69％。经大鼠灌胃杀虫双50mg／kg后，测定不同时相全血中沙蚕毒素含量。根据杀虫双在吸收前转化的模式，新编制了计算程序。经口灌胃后大鼠全血中沙蚕毒素浓度-时间曲线符合开放型二室模型。其浓度与时间关系如下：C=-6223.42e~(-5.35t)+35.28e~(-2.67t)+1.411e~(-0.35t)+6186.73e~(-5.37t)     

杀虫双在大鼠体内生物转化的研究

建立了大鼠胃、肠中杀虫双和沙蚕毒素的气相色谱定量测定方法。胃和肠中杀虫双平均回收率分别为９７．６％和１１６．２％，沙蚕毒素平均回收率分别为１０２．６％和９９．８％。采用此方法观察经口灌胃杀虫双后在大鼠体内转化成沙蚕毒素的部位以及其转化的动态变化。ＴＬＣ及ＧＣ定性、定量结果均表明胃是主要转化部位。给大鼠灌胃杀虫双（５．０ｍｇ／ｋｇ）１ｍｉｎ后，胃中杀虫双总量（杀虫双及２．３８倍的沙蚕毒素之和）与给药量相当，而此时约３０％杀虫双己转化成沙蚕毒素，给药１ｈ后，胃中未检出杀虫双和沙蚕毒素。杀虫双在胃中消失动态与时间呈良好线性关系。胃中杀虫双浓度与时间的关系为Ｃ＝５５．９８ｅ－０．２５ｔ＋４１．８５ｅ－０．０６ｔ     

杀虫双在动物体内的代谢研究 五、杀虫双代谢产物的分离与鉴定

经口灌胃给大鼠杀虫双77mg/kg和沙蚕毒素52mg/kg，分别收集6小时尿，采用层色谱（TLC）和气相色谱－质谱（GC－MS）分离和鉴定尿中主要代谢产物，给予杀虫双的鼠尿，经高效薄层色谱（HPTLC）分析，未检出杀虫双原形物，酶解也未见明显变化，经口给大鼠杀虫双或沙蚕毒素，鼠尿经HPTLC及GC－MS分析结果一致，据此推断，杀虫双和沙蚕毒素在大鼠体内代谢途径相同，杀虫双进入体内迅速转化成沙蚕毒素，继而在硫原子上甲基化和氧化，并在二甲胺部分进行脱甲基和水解。     

杀虫双在动物体内的代谢研究 三、杀虫双的高效薄层色谱法测定及其在大鼠体内的毒物代谢动力学研究

本文建立了高效薄层色谱测定大鼠血浆中杀虫双和沙蚕毒素的方法。以甲醇处理血浆样品,取上清液于高效硅胶板上点样,用甲醇-乙酸乙酯(5:4)展开,喷以钙黄绿素-氯化钯溶液,以薄层色谱扫描仪定量测定斑点荧光强度。血浆中加入杀虫双和沙蚕毒素,回收率分别为97.3±2.6％(n=5,CV=2.65％)和94.9±3.9％(n=5,CV=3.92％),检测限杀虫双为11.9ng,沙蚕毒素为5ng。大鼠静脉注射杀虫双后,血浆中立即检出沙蚕毒素。根据开放型二室模型数学公式计算杀虫双及沙蚕毒素代谢动力学各参数值。经口灌胃后,各时相血浆样品中均未检出杀虫双原形。除个别一小时血浆样品中检出低浓度沙蚕毒素外,其他样品中也未检出沙蚕毒素。     

杀虫双在动物体内的代谢研究——三、杀虫双的高效薄层色谱法测定及其在大鼠体内的毒物代谢动力学研究

本文建立了高效薄层色谱测定大鼠血浆中杀虫双和沙蚕毒素的方法。以甲醇处理血浆样品,取上清液于高效硅胶板上点样,用甲醇-乙酸乙酯(5:4)展开,喷以钙黄绿素-氯化钯溶液,以薄层色谱扫描仪定量测定斑点荧光强度。血浆中加入杀虫双和沙蚕毒素,回收率分别为97.3±2.6%(n=5,CV=2.65%)和94.9±3.9%(n=5,CV=3.92%),检测限杀虫双为11.9ng,沙蚕毒素为5ng。大鼠静脉注射杀虫双后,血浆中立即检出沙蚕毒素。根据开放型二室模型数学公式计算杀虫双及沙蚕毒素代谢动力学各参数值。经口灌胃后,各时相血浆样品中均未检出杀虫双原形。除个别一小时血浆样品中检出低浓度沙蚕毒素外,其他样品中也未检出沙蚕毒素。     

杀虫双在动物体内的代谢研究 四、杀虫双的气相色谱法测定及其在兔体内的毒物代谢动力学研究

本文建立了血浆中杀虫双及沙蚕毒素的GC-FPD测定方法。检测限(沙蚕毒素)为0.5ng。血浆中加入杀虫双和沙蚕毒素,回收率均在90%以上。兔静脉注射杀虫双30秒后,血浆中即可检出沙蚕毒素。杀虫双和沙蚕毒素在兔体内代谢动力学按二室拟合,求出各参数值。经口灌胃试验,血浆中未检出杀虫双和沙蚕毒素。     

杀虫双在动物体内的代谢研究 四、杀虫双的气相色谱法测定及其在兔体内的毒物代谢动力学研究

本文建立了血浆中杀虫双及沙蚕毒素的GC-FPD测定方法。检测限(沙蚕毒素)为0.5ng。血浆中加入杀虫双和沙蚕毒素,回收率均在90％以上。兔静脉注射杀虫双30秒后,血浆中即可检出沙蚕毒素。杀虫双和沙蚕毒素在兔体内代谢动力学按二室拟合,求出各参数值。经口灌胃试验,血浆中未检出杀虫双和沙蚕毒素。     

杀虫剂杀螟丹遗传毒性检测

目的探讨杀虫剂杀螟丹的遗传毒性。方法应用Ames试验、小鼠骨髓嗜多染红细胞微核试验、彗星试验对杀螟丹的遗传毒性进行评价。结果Ames试验中,TA97、TA98、TA100和TA102 4个标准菌株无论代谢活化或非代谢活化,皆为阴性结果;小鼠骨髓嗜多染红细胞微核试验的结果,与阴性对照组比较,差异无统计学意义;彗星试验结果显示,剂量100 mg/（kg·bw）时,尾长与溶剂对照组比较,差异有统计学意义（P〈0.05）,而其他评价指标与溶剂对照组比较,差异无统计学意义。结论经Ames试验、小鼠骨髓嗜多染红细胞微核试验、彗星试验,杀螟丹遗传毒性均为阴性。     

有机磷农药代谢产物分析的研究进展

长期低剂量接触有机磷农药(organophosphorus pesticides,OPs)可引起迟发性神经疾病,严重时有诱发突变和致癌作用.根据OPs的化学和毒理学性质,可以通过生物监测方法评价人体接触OPs的程度及其对健康可能产生的潜在影响.     

Concentrations of selective metabolites of organophosphorus pesticides in the United States population

We report population-based concentrations (stratified by age, sex, and composite race/ethnicity variables) of selective metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol; TCPY), chlorpyrifos methyl (TCPY), malathion (malathion dicarboxylic acid; MDA), diazinon (2-isopropyl-4-methyl-6-hydroxypyrimidine; IMPY), methyl parathion (para-nitrophenol; PNP), and parathion (PNP). We measured the concentrations of TCPY, MDA, IMPY, and PNP in 1997 urine samples from participants, aged 6-59 years, of the National Health and Nutrition Examination Survey, 1999-2000. We detected TCPY in more than 96% of the samples tested. Other organophosphorus pesticide metabolites were detected less frequently: MDA, 52%; IMPY, 29%; and PNP, 22%. The geometric means for TCPY were 1.77 microg/L and 1.58 microg/g creatinine. The 95th percentiles for TCPY were 9.9 microg/L and 8.42 microg/g creatinine. The 95th percentiles for MDA were 1.6 microg/L and 1.8 microg/g creatinine. The 95th percentiles for IMPY and PNP were 3.7 microg/L (3.4 microg/g creatinine) and 5.0 microg/L (4.2 microg/g creatinine), respectively. Multivariate analyses showed that children aged 6-11 years had significantly higher concentrations of TCPY than adults and adolescents. Similarly, adolescents had significantly higher TCPY concentrations than adults. Although the concentrations between sexes and among composite racial/ethnic groups varied, no significant differences were observed.     

杀虫双(单)在动物体内的代谢研究——二、~(35)S-杀虫双在大鼠体内的分布与排泄

农药杀虫双(单)为我国目前取代六六六重要品种。本实验采用~(35)S-杀虫双,对该农药在动物体内的分布与排泄作进一步研究。结果表明整体放射自显影图上各组织的显影与放射性测量结果基本相符。~(35)S-杀虫双最终代谢产物掺入含硫组织如软骨等。~(35)S-杀虫双与~3H-杀虫单在大鼠体内的分布与排泄无明显差别。     

Assessment of the exposure of pest control operators to organophosphorus pesticides. Organophosphorus pesticides in blood and alkyl phosphate metabolites in urine

Pest control operators usually spray pesticides in small areas such as a kitchen in a restaurant and are exposed to various pesticides, especially those of the organophosphorus (OP) type. In order to evaluate their occupational exposure to OP pesticides during the work, OP pesticides in blood and alkyl phosphate metabolites in urine of these operators were analyzed and the relationship between pesticide exposure and analytical results were studied. OP pesticides in blood were analyzed by gas chromatography with flame photometric detector (FPD-GC) after separation of phospholipid in blood with silicagel column chromatography. OP pesticides were not detected in any blood samples (the limit of detection was 1 ng/ml). Dimethylphosphate (DMP) and dimethylthiophosphate (DMTP), being urinary metabolites of OP pesticides, were analyzed by FPD-GC after benzyl derivatization. This method eliminated interfering peaks in gas chromatograms. The ratio of two isomeric derivatives of DMTP was found to be constant. Both DMP and DMTP of the exposed group were significantly higher than those of the non-exposed group, DMP being higher than DMTP. The ratio of DMP to DMTP in the fenitrothion-dichlorvos-exposed group was significantly higher than that in the fenitrothion-exposed group. It was considered that the ratio might reflect a result of pesticide exposure. The urinary metabolites of OP pesticides tended to become lower with the lapse of time since the last exposure. However, small amounts were detected in a few samples even 5 days after the last exposure.